The search for a protective vaccine against cholera suitable not only for adults but also for children and infants in developing countries is urgently needed. To address this issue, we have recently started a Phase I/II study of a live attenuated oral Vibrio cholerae O1 vaccine, Peru 15, in Bangladesh. In the ongoing trial, we are studying the safety and immunogenicity of Peru15 and are evaluating a few key immune responses: the vibriocidal response, and serum responses to the O1 lipopolysaccharide and cholera toxin. However, funds do not permit analysis of immune responses to other key antigens identified as part of our ongoing collaborative project under the International Collaborations in Infectious Disease Research (ICIDR) Program, focussed on determining the components of protective immunity to cholera. In this proposal, we have three SPECIFIC AIMS. In SPECIFIC AIM #1, we will determine serum mucosal immune responses to a key colonization factor of V. cholerae, TcpA, induced after immunization with Peru 15. In SPECIFIC AIM #2, we will use the antibody in lymphocyte supernatant or ALS assay to determine mucosal immune responses to LPS, CT and TcpA in the vaccinees. In SPECIFIC AIM #3, we will compare the serum and mucosal immune responses generated after vaccination with Peru15, to those occurring after natural cholera infection, measured in our ongoing ICIDR project. All of the assays will use samples already being obtained from Bangladeshi adults, children and infants in both the vaccine trial of Peru 15, as well as in our ongoing ICIDR project, so no new sample collection or human studies approvals will be needed. These studies will fill a key gap in the current evaluation of Peru15 by allowing the determination of key additional immune responses in vaccinees and comparison of those to individuals naturally infected with V. cholerae.